Is PRPS1 p.Arg96= (c.288G>A) pathogenic?

PRPS1 p.Arg96= (c.288G>A) is classified Benign/Likely benign in PRPS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-27). Rare (popmax 0.163%, eas); Associated with Charcot-Marie-Tooth disease X-linked recessive 5.

What condition is associated with PRPS1 p.Arg96= (c.288G>A)?

PRPS1 p.Arg96= (c.288G>A) is associated with Charcot-Marie-Tooth disease X-linked recessive 5, phosphoribosylpyrophosphate synthetase superactivity, Arts syndrome (ClinVar).

How common is PRPS1 p.Arg96= (c.288G>A) in the general population?

PRPS1 p.Arg96= (c.288G>A) is rare (popmax 0.163%, eas) (gnomAD).

How is X-linked Charcot-Marie-Tooth disease type 5 inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRPS1 p.Arg96=

c.288G>A · rs752194539 · VCV382624

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

Conditions

Charcot-Marie-Tooth disease X-linked recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.4, phastCons 1
Overall
CADD	7.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% East Asian · 55/33,798 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00463% 56/1,209,934 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.0021%	47,595

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRPS1
Protein: p.Arg96=
Coding: c.288G>A
MANE Select: NM_002764
dbSNP: rs752194539
Type: single nucleotide variant
Location: chrX:107639460 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 96: a binding site; a turn

Full PRPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease X-linked recessive 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: phosphoribosylpyrophosphate synthetase superactivity Arts syndrome hearing loss, X-linked 1

For X-linked Charcot-Marie-Tooth disease type 5 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PRPS1 p.Arg96Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
PRPS1 p.Arg96Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PRPS1 p.Arg214Trp Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Asn114Ser Likely pathogenic ★★ ⚠ same condition
PRPS1 p.Ile107Val Likely pathogenic ★★ same condition
PRPS1 p.Met115Thr Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Met115Val Pathogenic/Likely pathogenic ★★ same condition
PRPS1 c.306+5G>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prps1-p-arg96 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown